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Regulation of Renal Angiotensin Converting Enzyme 2 (ACE2) Activity by Angiotensin II (AngII)
Author(s) -
Liu Jun,
Ji Hong,
Kraus Carl,
Zheng Wei,
Wu Xie,
Sandberg Kathryn
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1019.23
Subject(s) - angiotensin ii , angiotensin converting enzyme 2 , medicine , endocrinology , kidney , chemistry , renin–angiotensin system , angiotensin converting enzyme , angiotensin 1 , enzyme , blood pressure , biochemistry , covid-19 , disease , infectious disease (medical specialty)
ACE2 is a monocarboxypeptidase that counteracts the vasoconstrictor effects of AngII by converting AngII to Ang[1‐7] in kidney and other tissues. We studied renal ACE2 in AngII‐induced hypertension in male (M) and female (F) mice after developing a sensitive assay for ACE2 activity in the mouse kidney. While no sex differences were found in ACE2 Km, under control (Ctr) conditions, ACE2 Vmax (maximum enzyme velocity) was 1.9‐fold greater in M vs F [relative fluorescence units (RFU): M‐Ctr, 1550±16 vs F‐Ctr, 823±120, p<0.0001]. After AngII infusion (800 ng/min/kg x 7d), ACE2 Vmax was increased in both sexes though the magnitude of this increase was greater in F [RFU: M‐AngII, 1890±87 vs F‐AngII, 1200±58, n=5; p<0.0001]; AngII increased renal ACE2 activity by 22% in M vs 45% in F. Mean arterial pressure (MAP) was measured by radiotelemetry. After AngII infusion, peak MAP was higher in M vs F mice [MAP (mm Hg): M‐AngII, 145±5.5 vs F‐AngII, 132±3.8]. This study demonstrates that renal ACE2 activity is up‐regulated by infusing the AngII substrate in both sexes. Up‐regulation of renal ACE2 may be a compensatory feedback mechanism for counteracting the increase in plasma AngII and MAP induced by AngII infusion. The finding that the magnitude of this effect is greater in F vs M raises the possibility that these differences in renal ACE2 feedback contribute to why M mice have higher MAP than F after AngII infusion (R01 AG19291).